Preparing your results

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

CCDC103 mutations cause primary ciliary dyskinesia by disrupting assembly of ciliary dynein arms.

Cilia are essential for fertilization, respiratory clearance, cerebrospinal fluid circulation and establishing laterality. Cilia motility defects cause primary ciliary dyskinesia (PCD, MIM244400), a disorder affecting 1:15,000-30,000 births. Cilia motility requires the assembly of multisubunit dynein arms that drive ciliary bending. Despite progress in understanding the genetic basis of PCD, mutations remain to be identified for several PCD-linked loci. Here we show that the zebrafish cilia paralysis mutant schmalhans (smh(tn222)) encodes the coiled-coil domain containing 103 protein (Ccdc103), a foxj1a-regulated gene product. Screening 146 unrelated PCD families identified individuals in six families with reduced outer dynein arms who carried mutations in CCDC103. Dynein arm assembly in smh mutant zebrafish was rescued by wild-type but not mutant human CCDC103. Chlamydomonas Ccdc103/Pr46b functions as a tightly bound, axoneme-associated protein. These results identify Ccdc103 as a dynein arm attachment factor that causes primary ciliary dyskinesia when mutated.

Pubmed ID: 22581229


  • Panizzi JR
  • Becker-Heck A
  • Castleman VH
  • Al-Mutairi DA
  • Liu Y
  • Loges NT
  • Pathak N
  • Austin-Tse C
  • Sheridan E
  • Schmidts M
  • Olbrich H
  • Werner C
  • H√§ffner K
  • Hellman N
  • Chodhari R
  • Gupta A
  • Kramer-Zucker A
  • Olale F
  • Burdine RD
  • Schier AF
  • O'Callaghan C
  • Chung EM
  • Reinhardt R
  • Mitchison HM
  • King SM
  • Omran H
  • Drummond IA


Nature genetics

Publication Data

June 1, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK053093
  • Agency: NIDDK NIH HHS, Id: F32DK083868
  • Agency: NIGMS NIH HHS, Id: GM051293
  • Agency: NIDCR NIH HHS, Id: R01 DE016779
  • Agency: NIDDK NIH HHS, Id: R01 DK053093
  • Agency: NIGMS NIH HHS, Id: R01 GM056211
  • Agency: Medical Research Council, Id:
  • Agency: Wellcome Trust, Id:

Mesh Terms

  • Animals
  • Cilia
  • Dyneins
  • Female
  • Humans
  • Kartagener Syndrome
  • Male
  • Mutation
  • Pedigree
  • Zebrafish